Heart failure is a chronic progressive disease. In the United States, there are 5 million patients with heart failure. Approximately 550,000 new cases are diagnosed and more that 285,000 deaths occur annually from heart failure indicating that the number of heart failure patients is on the rise.
Dystrophin-deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy (See, e.g., Muntoni, Curr Opin Neurol 16, 577-83 (2003)). Heart failure accounts for an estimated 15% of the fatalities in DMD (See, e.g., Emery, A. E. H. in Duchenne Muscular Dystrophy (ed. Emery, A. E. H.) (Oxford University Press, Oxford, 2003)). Progress toward defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscles, with comparatively little attention directed at cardiac muscle.
The pathophysiological mechanisms involved in cardiac myocytes are likely to differ significantly from skeletal myofibers, as underscored by significant cardiac disease in patients with truncated or reduced levels of dystrophin without skeletal muscle disease (See, e.g., Finsterer and Stollberger, Cardiology 99, 1-19 (2003)). Thus, several fundamental questions regarding the consequences of dystrophin-deficiency in cardiac muscle remain unanswered. Notably, it is unknown whether dystrophin-deficiency directly causes altered force transmission and/or membrane fragility in cardiac muscle at the single myocyte level.
There exists a need for new compositions and new methods for treating heart disease in general, as well as heart disease related to dystrophic cells, tissues and subjects, and for preventing and/or correcting the underlying bases of pathogenesis in subjects with heart disease (e.g., generally as well as in dystrophic subjects).